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Two-electrode voltage clamp using microelectrodes
The two-electrode voltage clamp (TEVC) technique is used to study properties of membrane proteins, especially ion channels. Researchers use this method most commonly to investigate membrane structures expressed in Xenopus oocytes. The large size of these oocytes allows for easy handling and manipulability.

The TEVC method utilizes two low-resistance pipettes, one sensing voltage and the other injecting current. The microelectrodes are filled with conductive solution and injected into the cell membrane to artificially control membrane potential. The membrane acts as a dielectric as well as a resistor, while the fluids on either side of the membrane function as capacitors. The microelectrodes compare the membrane potential against a command voltage, giving an accurate reproduction of the currents flowing across the membrane. Current readings can then be used to analyze the electrical response of the cell to different applications.

This technique is favored over single-microelectrode clamp or other voltage clamp techniques when conditions call for resolving large currents. The high current-passing capacity of the two-electrode clamp makes it possible to clamp large currents that are impossible to control with single-electrode patch techniques. The two-electrode system is also desirable for its fast clamp settling time and low noise. However, TEVC is limited in use with regard to cell size. It is effective in larger-diameter oocytes, but more difficult to use with small cells. Additionally, TEVC method is limited in that the transmitter of current must be contained in the pipette. It is not possible to manipulate the intracellular fluid while clamping, which is possible using patch clamp techniques. Another disadvantage involves "space clamp" issues. Cole's voltage clamp used a long wire that clamped the squid axon uniformly along its entire length. TEVC microelectrodes can provide only a spatial point source of current that may not uniformly affect all parts of an irregularly shaped cell.

Dual-cell voltage clamp
The dual-cell voltage clamp technique is a specialized variation of the two electrode voltage clamp, and is only used in the study of gap junction channels. Gap junctions are pores that directly link two cells through which ions and small metabolites flow freely. When two cells in which gap junction proteins are expressed either endogenously or via injection of mRNA, a junction channel will form between the cells. Since two cells are present in the system, two sets of electrodes are used. A recording electrode and a current injecting electrode are inserted into each cell, and each cell is clamped individually (each set of electrodes is attached to a separate apparatus, and integration of data is performed by computer). To record junctional conductance, the current is varied in the first cell while the recording electrode in the second cell records any changes in Vm for the second cell only. (The process can be reversed with the stimulus occurring in the second cell and recording occurring in the first cell.) Since no variation in current is being induced by the electrode in the recorded cell, any change in voltage must be induced by current crossing into the recorded cell, through the gap junction channels, from the cell in which the current was varied.